Samenvatting
De laatste jaren is significante vooruitgang geboekt in het onderzoek naar genen die betrokken zijn bij de normale geslachtsontwikkeling en hoe mutaties in deze genen leiden tot een stoornis in dit proces. Tevens is inzicht verkregen in het ontstaan van kiemceltumoren, die met een verhoogde frequentie voorkomen bij patiënten met bepaalde vormen van een gestoorde geslachtsontwikkeling. Tegelijk is de gangbare nomenclatuur en classificatie herzien. Dit artikel biedt een overzicht van de geslachtsontwikkeling en een update over de kennis van de genen die betrokken zijn bij, en aanleiding kunnen geven tot, een abnormaal verloop van dit proces. De vernieuwde nomenclatuur en classificatie, gebruikt sinds 2006, worden toegelicht. Ten slotte wordt het risico op de ontwikkeling van kiemceltumoren bij de verschillende vormen van deze aandoeningen besproken en wordt beschreven hoe recent onderzoek erin geslaagd is een risicoanalyse mogelijk te maken.
Vanuit psychologisch perspectief wordt de laatste jaren in toenemende mate het belang benadrukt om bij ernstige ondervirilisatie waar mogelijk te kiezen voor de mannelijke genderidentiteit. Patiëntenbelangenverenigingen pleiten voor een meer conservatief beleid met betrekking tot gonadectomie; er lijkt een vernieuwde interesse te groeien bij artsen, wetenschappers en overheidsinstanties voor het opzetten van internationale studies en samenwerkingsverbanden om het beleid bij patiënten met een gestoorde geslachtsontwikkeling te optimaliseren. De verwachting is dan ook dat al deze factoren samen in de komende jaren zullen leiden tot nieuwe richtlijnen met betrekking tot de optimale zorg voor patiënten bij wie de geslachtsontwikkeling abnormaal is verlopen.
Summary
In recent years, considerable progress has been made in the characterization of genes involved in normal sex development, and in how mutations in these genes may lead to abnormalities in this process. Moreover, promising results have been obtained in the research concerning the development of germ cell tumors in these patients. At the same time, the commonly used nomenclature and classification system describing the various forms of disorders of sex development has been revised. This article summarizes our actual knowledge with regard to normal sex development and the various genes that are involved in this process and describes how mutations in these genes may lead to a disturbed process of sex development. The renewed nomenclature and classification system, which are in use since 2006, are explained; finally the risk for the development of germ cell tumors in patients with disorders of sex development is discussed, and it is shown how recent research has offered tools to estimate the risk in the individual patient.
Psychological research is increasingly emphasizing the importance to consider male gender identity wherever possible in cases of severe undervirilization. Patient advocacy groups demand a more conservative approach with regard to gonadectomy. Medical doctors, scientists, as well as governmental instances are increasingly interested in the development of international research protocols and collaborations in order to optimize the management of patients with disorders of sex development in the future. As a consequence, it is expected that new guidelines for the optimal care of these patients will be proposed in the coming years.
Notes
Primitieve organisatie van kiemcellen en gepolariseerde sertolicellen, gekenmerkt door activatie van SOX9.
Ook wel POU5F1 genoemd.
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Mw. dr. M. Cools, afdeling Pediatrie, Universitair Ziekenhuis Gent. Dhr. prof. dr. L.H.J. Looijenga, afdeling Pathologie, Josephine Nefkens Instituut, Erasmus MC, Rotterdam. Dhr. dr. B.J. Otten, subafdeling Kinderendocrinologie, UMC St Radboud, Nijmegen. Mw. drs. K.P. Wolffenbuttel, afdeling Urologie, dhr. prof. dr. S.L.S. Drop, subafdeling Endocrinologie, Sophia Kinderziekenhuis, Erasmus MC, Rotterdam.
Correspondentieadres: Martine Cools, afdeling Pediatrie, Dienst Kinderendocrinologie, Universitair Ziekenhuis Gent, Gebouw 5K6, De Pintelaan 185, 9000 Gent, tel: 09-2404728
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Cools, M., Looijenga, L.H.J., Otten, B.J. et al. Genetische basis, terminologie en het risico voor de ontwikkeling van kiemceltumoren bij stoornissen in de geslachtsontwikkeling. KIND 76, 92–104 (2008). https://doi.org/10.1007/BF03078187
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DOI: https://doi.org/10.1007/BF03078187